The long term objectives of the proposed research are to gain a better understanding of the mechanisms of dental caries and to provide rational bases for improved preventive or therapeutic regimens. The Principal Investigator proposes to do basic studies of the anomalous solubility behavior of carbonated apatites (CAPs) and human dental enamel (HE) with the general objective of establishing how the solubility depends on the composition of the mineral phase, the crystallinity of the mineral phase, an the composition of the external dissolution medium. The studies will rely heavily on the metastable equilibrium solubility (MES) distribution paradigm and the surface complex hypothesis developed just prior to the beginning of the past project period. The MES and the surface complex concepts have dictated entirely new approaches to both experimental design and data interpretation and have provided the framework for understanding the interrelationship between mineral composition, mineral crystallinity, solution composition and the observed solubility of biominerals and synthetic apatites. There are four specific aims. Aim 1 proposes studies to establish for the CAPs the quantitative relationships between the magnitude of the MES, the CAP crystallinity (especially crystallite microstrain), and carbonate content, and the stoichiometry of the MES governing surface complex. In Aim 2, studies are proposed to quantitatively establish the influence of solution foreign ions (strontium and fluoride) on the magnitude of the MES and the stoichiometry of the MES governing surface complex. In Aim 3, studies are proposed to quantitatively establish the possible crystal lattice effects of these foreign ions on the magnitude of the MES. Aim 4 proposes to establish the relevance of the findings in the CAP studies (above) to the solubility behavior of HE. Two major experimental breakthroughs of the past project period make it possible for accomplishing these aims. The first of these is a procedure of relatively high accuracy for deducing the dissolution driving force function (and therefore the stoichiometry of the MES governing surface complete) from analysis of the MES distribution data obtained as a function of several independent variables (e.g., buffer pH, solution common ions, and solution foreign ions). The other is a procedure for separating and quantifying the contributions of crystallite size and microstrain to CAP crystallinity using X-ray diffraction data and the Rietveld method of whole-pattern-fitting structure-refinement. Taken together, these two methods permit addressing the questions associated with each of the Specific Aims.